Malabsorption of dietary vitamin D and enterohepatically circulating vitamin metabolites is important in the pathogenesis of vitamin D deficiency in patients with gastrointestinal disorders. We propose to study the mechanism and pathway of intestinal absorption of vitamin D and vitamin D metabolites, emphasizing factors influencing absorption which may be altered in gastrointestinal disease. Intestinal absorption experiments will be performed in rats with thoracic and bile duct cannulae to study the effects of intraluminal factors such as bile salts, fatty acids and monoglyceride, and phosphalipids on absorption of vitamin D sterols. Lymph from rats given vitamin D sterols will be analyzed by Sephadex LH-20 and high pressure liquid chromatography to determine if vitamin D sterols are metabolized during absorption. We propose to assess the role of chylomicrons in absorption of vitamin D metabolites by measuring the distribution of vitamin D sterols in lymph lipoproteins separated by ultracentrifugation, and by examining the effect of cyclohe, a protein synthesis inhibitor, on absorption. Absorption of vitamin D metabolites in jejunum and ileum will be compared. We plan to determine the pathway of release of vitamin D sterols from the intestine by quantitating the absorbed vitamin recovered in lymph and portal blood. The potential role of the serum vitamin D binding protein in influencing vitamin release will be studied by measuring exchange of vitamin between chylomicrons and vitamin D binding protein in vitro and by using a system of vascular perfusion of the rat small intestine to determine the effect of binding protein concentration on vitamin D release into the portal circulation. We also propose a clinical study comparing intestinal absorption of vitamin D and 25(OH) vitamin D in patients with cholestatic liver disease and ileal resection.